6. Project Summary/Abstract Traumatic brain injury (TBI) is a leading cause of morbidity and disability in service members deployed in Iraq and Afghanistan, accounting for one-fourth of medical evacuations. An explosive mechanism was linked to 78% of the clinician-confirmed injuries sustained by U.S. service members over a three-year period, and the head and neck were involved in 30% of these injuries. To elucidate the neural mechanisms mediating cognitive deficit after blast related TBI, we propose to perform multimodality brain imaging, cognitive, behavioral and health related quality of life outcome measures in veterans and service members who sustained TBI due to blast while deployed in Iraq or Afghanistan. A total of 84 veterans and service members will be enrolled between 4 and 60 months post-injury, including 28 who sustained moderate to severe blast related TBI, 28 with mild blast related TBI, and a comparison group who sustained injury not involving the brain. Functional magnetic resonance imaging (fMRI) will be performed during cognitive control and working memory tasks and analyzed in relation to the integrity of brain gray matter and white matter measured by magnetization transfer imaging and diffusion tensor imaging and brain region volumes measured by magnetic resonance imaging (MRI). We will also analyze fMRI data adjusting for co-morbid posttraumatic stress disorder and depression symptoms. With this design we propose to evaluate the effects of blast related TBI on brain function in relation to indices of brain structural integrity and co-morbidities of injury.